Landscape of transcription in human cells

Centre for Genomic Regulation and UPF, Doctor Aiguader 88, Barcelona 08003, Catalonia, Spain.
Nature (Impact Factor: 41.46). 09/2012; 489(7414):101-8. DOI: 10.1038/nature11233
Source: PubMed


Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.

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Available from: Igor Antoshechkin, Feb 17, 2014
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    • "Mammalian genomes are more extensively transcribed than expected, giving rise to thousands of long non-coding RNAs (lncRNAs), which are defined as RNA transcripts non-coding for protein and longer than 200 nt (Bertone et al., 2004; Birney et al., 2007; Carninci et al., 2005; Cheng et al., 2005; Djebali et al., 2012; Kapranov et al., 2007; Yelin et al., 2003). Among lncRNAs, NATs have emerged as a large class of regulatory long ncRNAs (Faghihi and Wahlestedt, 2009; Magistri et al., 2012). "
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    ABSTRACT: Long non-coding RNAs (lncRNAs), including natural antisense transcripts (NATs), are expressed more extensively than previously anticipated and have widespread roles in regulating gene expression. Nevertheless, the molecular mechanisms of action of the majority of NATs remain largely unknown. Here, we identify a NAT of low-density lipoprotein receptor-related protein 1 (Lrp1), referred to as Lrp1-AS, that negatively regulates Lrp1 expression. We show that Lrp1-AS directly binds to high-mobility group box 2 (Hmgb2) and inhibits the activity of Hmgb2 to enhance Srebp1a-dependent transcription of Lrp1. Short oligonucleotides targeting Lrp1-AS inhibit the interaction of antisense transcript and Hmgb2 protein and increase Lrp1 expression by enhancing Hmgb2 activity. Quantitative RT-PCR analysis of brain tissue samples from Alzheimer's disease patients and aged-matched controls revealed upregulation of LRP1-AS and downregulation of LRP1. Our data suggest a regulatory mechanism whereby a NAT interacts with a ubiquitous chromatin-associated protein to modulate its activity in a locus-specific fashion. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 04/2015; 11(6). DOI:10.1016/j.celrep.2015.04.011 · 8.36 Impact Factor
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    • "Thus, it has been speculated, that ncRNAs might regulate development and consequently also brain function in humans (Mattick 2011). While ∼75% of the human genome is transcribed into RNA, the majority of these RNA transcripts lack proteincoding potential (Djebali et al. 2012) and thus might represent regulatory ncRNAs (Birney et al. 2007; Washietl et al. 2007). In the past, various ncRNA species have been shown to exhibit essential functions in the regulation of gene expression , thereby also playing key roles in neural development, neural plasticity, and brain aging (Mattick 2011). "
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    RNA 10/2014; 20(12). DOI:10.1261/rna.047225.114 · 4.94 Impact Factor
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    • "The alignment rate for the six samples varied, ranging from 38.67% for F4 to 47.26% for M4. In this study, the percent uniquely aligned reads is lower than in studies performed by Eizirik et al. and Djebali et al. in humans [29], [30], and slightly lower than the results of Li et al. in chickens [31]. This may be due to the fact that the duck genome is only a draft, and requires more work to improve it to the level of chicken or human. "
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